Prostacyclin is a topical hormone produced mainly on an inner vessel wall of arterial duct of a living body, and due to its high physiological activities such as the platelet aggregation inhibiting activity and the vasodilating activity, it is an essential factor for adjusting the functions of a living body. An attempt has been made to provide it directly as a medicament (P. J. Lewis & J. O. Grady' Clinical Pharmacology of Prostacyclin' Raven Press, N. Y., 1981).
Since, however, natural prostacyclin has, in its molecule, an enol ether bond which is easily hydrolyzable, it is easily deactivated under neutral or acidic conditions, and it cannot be said to be a preferred compound as a medicament due to its chemical instability. Therefore, chemically stable synthetic prostacyclin derivatives having physiological activities equivalent to those of natural prostacyclin have been studied at home and abroad (see R. C. Nickolson, et al, Medicinal Research Reviews, Vol. 5, page 5, 1985). Among these derivatives, isocarbacyclin obtained by replacing oxygen atoms in the 6 and 9 positions of prostacyclin with methylene group (--CH.dbd. group) and converting double bonds in the 5 and 6 positions to single bonds is a derivative which is highly chemically stable and has bioactivities equivalent to those of natural prostacyclin, and studies are under way to apply it to a medicament.
On the other hand, as compounds prepared by stabilizing prostaglandins as fat preparations, fat emulsions containing PGE1 and PGA1 have been proposed in recent years for the purpose of vasodilation activity, platelet aggregation inhibition and depression activity [see Japanese Laid-open Patent Publications Nos. 222014/1983 and 141518/1984, and Ann. Rheum. Diseases, 41 263 (1982); Journal of Pharmacy and Pharmacology, 35, 398 (1983)]. It is also proposed to apply this method to an anticancer agent for increasing the selective targeting of the anticancer agent on a target organ (see Japanese Laid-open Patent Publication No. 122423/1984). However, it has been difficult to prepare prostacyclin into a fat emulsion due to its chemical instability. Attempts have therefore been made to prepare the above isocarbacyclins into fat emulsions, and there have been developed stable preparations having durability in activity, having a targeting effect and having an increased effect (Japanese Laid-open Patent Publication No. 289034/1986).
Meanwhile, it has been studied to apply natural prostacyclin to the therapy of cerebral thrombosis due to its pharmacological effect (see Hsu C. Y. et al, Stroke, Vol. 18, page 352, 1987). However, its activities are not sufficient, and its side effects are problems. Therefore, for overcoming the above defects, Mizushima et al, have attempted to administer preparations of fat emulsions of the above isocarbacyclins to patients having cerebral thrombosis but showing relatively stable symptoms at a chronic stage (see Prostaglandins, Vol. 40, page 155, 1990).